title: Stratification of patients is the way to go to develop neuroprotective/disease-modifying drugs for Alzheimer's disease.
abstract: Development of effective neuroprotective drugs for Alzheimer's disease (AD) is a formidable challenge because this disease is multifactorial and heterogeneous. Although AD is characterized histopathologically by the presence of numerous amyloid-beta plaques and neurofibrillary degeneration of abnormally hyperphosphorylated tau in the brain, these two hallmark lesions do not exist in any fixed proportion in this disease. Furthermore, in the brains of some normal aged individuals, there are as many amyloid-beta plaques seen as in typical cases of AD. On the other hand, extensive neurofibrillary degeneration of abnormally hyperphosphorylated tau and dementia but in the absence of amyloid-beta plaques occur in several related neurodegenerative disorders called tauopathies. More than one molecular mechanism has been described for the development of amyloid-beta as well as neurofibrillary degeneration of abnormally hyperphosphorylated tau. Thus, AD apparently results from several different etiopathogenic mechanisms and offers numerous rational therapeutic targets. We have discovered that there are at least five different subgroups of AD, and future studies are likely to identify additional subgroups. The employment of these subgroups of AD in clinical trials can markedly increase the success in developing specific and potent therapeutic drugs.
authors.affiliation: Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, New York, NY 10314, USA. iqbalk@worldnet att.net
authors.forename: Khalid
authors.initials: K
authors.lastname: Iqbal
authors.forename: M Omar
authors.initials: MO
authors.lastname: Chohan
authors.forename: Inge
authors.initials: I
authors.lastname: Grundke-Iqbal
mesh_terms: D000544:Alzheimer Disease / Q000145:classification / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics; D002986:Clinical Trials as Topic; D006801:Humans; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D018579:Patient Selection; D012107:Research Design
chemical_list: D018696:Neuroprotective Agents